Evaluating the Therapeutic Potential of Focal Electrically Administered Seizure Therapy (FEAST) in the Treatment of Depression: A Multicenter Randomized Clinical Trial

Registry record from ClinicalTrials.gov (NCT07857122). This is a study registration, not published results. Lead sponsor: Centre Hospitalier St Anne. Recruitment status: NOT_YET_RECRUITING. Phase: NA. Study type: INTERVENTIONAL. Enrollment: 108 participants (ESTIMATED). Conditions: Major Depressive Episode (MDE), Unipolar Disorder, Bipolar 1 Disorder. Interventions: DEVICE: Stimulation by the Sigma ECT/FEAST device; DEVICE: Stimulation by Sigmastim ECT 200J device administered in right unilateral (RUL); DEVICE: Stimulation by Sigmastim ECT 200J device administered in bilateral (BT). Primary outcome measures: Change from baseline in the Q-LES-Q-SF score at Day 5 , From enrollment to the 5 days after the last session of the acute phase treatment (Day 5). Brief summary: A significant proportion of patients remain resistant to antidepressant therapies, even when treatment is well managed. Electroconvulsive therapy (ECT) is a well-established method for treating certain severe and resistant psychiatric pathologies. ECT is also the gold standard for treating mood disorders. Although effective, it is associated with cognitive side effects (memory impairment, post-ECT confusion, longer reorientation time), particularly with bitemporal (BT) montage and brief pulse stimulation. These effects may contribute to patient reluctance and limit adherence to this therapy. From a mechanistic point of view, ECT causes changes in cerebral blood flow (rCBF) and brain electrical activity, particularly in the prefrontal cortex, where the induction of "pseudo-epileptic seizures" appears to be related to therapeutic efficacy, while cognitive side effects appear to be associated with alterations in the temporal areas. The conventional stimulation method results in widespread diffusion of the current due to the properties of the skull, limiting control over the distribution of intracerebral charge densities. In this context, a new approach called "Focal Electrically Administered Seizure Therapy" (FEAST) has been developed to focus the electrical current and limit cognitive side effects. Unlike traditional ECT, FEAST uses unidirectional current and optimized electrode placement, aiming to induce seizures in a more localized manner in the right prefrontal cortex while reducing propagation to temporal regions. The FEAST configuration is based on scientific literature (protocols, parameters, electrode positioning) and not on a "pre configured" mode validated by the medical device manufacturer. Neuroimaging studies suggest that FEAST causes an increase in blood flow in the right prefrontal cortex at the onset of the seizure, followed by a postictal redistribution similar to that observed with ECT, confirming its targeted effect. Open-label clinical trials conducted to date show that FEAST significantly improves depressive symptoms with a more favorable cognitive profile compared to traditional ECT, notably by reducing the impact on autobiographical memory and decreasing the time needed to regain orientation acutely after treatment. Several comparative studies between FEAST and unilateral ultra-brief pulse ECT suggest an advantage in terms of cognitive tolerance, although the differences are not always statistically significant. A multicenter trial also showed comparable effects on reducing suicidal ideation, suggesting that FEAST could be an alternative to traditional ECT. Indeed, preliminary studies indicate that FEAST may offer similar benefits to ECT in terms of reducing depressive symptoms, but with fewer cognitive side effects, which could lead to a better quality of life. Although these studies are promising, they remain few in number and have methodological limitations (open-label clinical trials, feasibility studies, lack of randomization with a comparator arm, small sample size, or assignment to the study arm based on patient preference). There are currently no other randomized clinical trials on FEAST underway or in preparation worldwide. Well-designed, multicenter clinical trials with sufficient patient numbers to achieve satisfactory statistical power are therefore needed to address the limitations of previous studies and explore the clinical benefits of FEAST. The present study is therefore a randomized, multicenter, double-blind clinical trial designed to evaluate the superiority of FEAST in terms of safety and efficacy compared to traditional ECT modalities.